a) Field of the Invention
The present invention relates to a process for the industrial preparation of quinone derivatives such as for example 2-[4'-(p-nitrophenoxy)-3'-methyl-2'-butenyl]-3,5,6-trimethyl-1,4-benzoquin one, and novel intermediates.
There are many useful chroman derivatives, as pharmaceuticals, including at first 5-[{4-[3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyrane-2-yl)met hoxy]phenyl}methyl]-2,4-thiazolidinedion (Code Name: CS-045, GAS Registry No.97322-87-7) which is a blood suger lowering agent. For the preparation of these chroman derivatives, there are generally used, as intermediate, 2-[4'-(p-nitrophenoxy)-3'-methyl-2'-butenyl]-3,5,6-trimethyl-1,4-benzoquin one.
b) Description of the Related Art
Conventionally, EP-543,346, for example, discloses the preparation of 2-[4'-(p-nitrophenoxy)-3'-methyl-2'-butenyl]-3,5,6-trimethyl-1,4-benzoquin one (XII) which comprises condensing 3,5,6-trimethyl-1,4-hydroxyquinone (VIII) and 1-chloro-2-methyl-3-butene-2-ol (IX) in accordance with a Friedel-Crafts reaction, then oxidizing the resulting condensate (X), and followed by adding p-nitrophenol to the oxidized condensate (XI). This preparation process will be described, as follows, where X means a halogen atom. ##STR2##
According to the process described in EP-543,346, 3,5,6-trimethyl-1,4-hydroquinone (VIII) and an allyl halide such as 1-chloro-2-methyl-2-butene-3-ol (IX) are utilized. However, since such an allyl halide has a very high reactivity, it will produce many decomposites and other structural isomers, and it is therefore difficult to purify the object compound. Furthermore, the allyl halide is unstable and hence, it must be prepared in situ, with some problems in the operationally safe point of view, for instance, its stimulation and the like.
2-(1-Chloro-2-methyl-2-butene-4-yl)-3,5,6-trimethyl-1,4-hydroquinone (X) obtained in accordance with the Friedel-Crafts condensation and 2-(1-chloro-2-methyl-2-butene-4-yl)-3,5,6-trimethyl-1,4-quinone (XI) obtained by oxidizing said hydroquinone (X) are also unstable. Accordingly, they will produce many decomposites and by-products in their respective reaction steps, and it is therefore difficult to purify the object compound, with a lower yield accompanied therewith. Namely, it can not be concluded that this process of the prior art is an industrially proper process.
As mentioned above, there has not been an industrially excellent preparation process capable of preparing 2-[4'-(p-nitrophenoxy)-3'-methyl-2'-butenyl]-3,5,6-trimethyl-1,4-benzoquin one (XII) useful as pharmaceutical intermediates, at a high yield and with safety.